1,2-Dichloroethane → 1-9H-fluoren-9-ylmethyl (2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-{[5-oxo-5-(1-piperidinyl)pentanoyl]amino}butyl(3-iodobenzyl)carbamate

HRID 1350967Notes

Reaction equation

HRID 1350967 reaction equation
C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.NC(C1C=[C:20]([CH:24]=[C:25]([C:27]([N:29]([CH2:33][CH2:34][CH3:35])[CH2:30][CH2:31]C)=[O:28])C=1)[C:21]([OH:23])=O)=O.Cl.[NH2:37][C@@H:38]([CH2:68][C:69]1[CH:74]=[C:73]([F:75])[CH:72]=[C:71]([F:76])[CH:70]=1)[C@H:39]([OH:67])[CH2:40][N:41]([CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[C:62]([I:66])[CH:61]=1)[C:42](=[O:58])[O:43][CH2:44][CH:45]1[C:57]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[C:51]2[C:46]1=[CH:47][CH:48]=[CH:49][CH:50]=2.CN1CCOCC1>CN(C=O)C>[F:76][C:71]1[CH:70]=[C:69]([CH2:68][C@H:38]([NH:37][C:21](=[O:23])[CH2:20][CH2:24][CH2:25][C:27](=[O:28])[N:29]2[CH2:30][CH2:31][CH2:35][CH2:34][CH2:33]2)[C@H:39]([OH:67])[CH2:40][N:41]([CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[C:62]([I:66])[CH:61]=2)[C:42](=[O:58])[O:43][CH2:44][CH:45]2[C:46]3[CH:47]=[CH:48][CH:49]=[CH:50][C:51]=3[C:52]3[C:57]2=[CH:56][CH:55]=[CH:54][CH:53]=3)[CH:74]=[C:73]([F:75])[CH:72]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 223948913-Carbamoyl-5-dipropylcarbamoyl-benzoic acidHCID 865858561-9H-fluoren-9-ylmethyl(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3-iodobenzyl)carbamate hydrochloride

Product 1

HCID 587598521-9H-fluoren-9-ylmethyl (2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-{[5-oxo-5-(1-piperidinyl)pentanoyl]amino}butyl(3-iodobenzyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HOBt (81 mg, 0.6 mmole) and EDC (105 mg, 0.55 mmole) are added to 1-carboxy-5-piperdinylglutaramide (IX, 100 mg, 0.5 mmole) in DMF (2 ml). The acid is activated 60 minutes then treated with 1-9H-fluoren-9-ylmethyl (2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3-iodobenzyl)carbamate hydrochloride (XXXV, EXAMPLE 590, 300 mg, 0.43 mmole) and NMM (0.19 ml, 1.72 mmole). The reaction is stirred 3 hours then concentrated under reduced pressure. The residue is partitioned between ethyl acetate and saturated aqueous bicarbonate. The organic phases are washed with aqueous potassium bisulfate, saline, dried over sodium sulfate and finally concentrated under reduced pressure to give crude product. Purification via flash chromatography with ethyl acetate/hexane (50/50) then methanol/ethyl acetate (10/90) gives the title compound, M+H=838.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. customThe residue is partitioned between ethyl acetate and saturated aqueous bicarbonate
  3. washThe organic phases are washed with aqueous potassium bisulfate, saline
  4. dry with materialdried over sodium sulfate
  5. concentrationfinally concentrated under reduced pressure
  6. customto give crude product
  7. customPurification via flash chromatography with ethyl acetate/hexane (50/50)

Sources & evidence

ORD record
ord-0ae297561c6743768b69071a2c8d6c9c
Source dataset
uspto-grants-2007_05
Patent number
US07214715B2

Reaction notes

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